This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The relationship between public transport use and acquisition of acute respiratory
infection (ARI) is not well understood but potentially important during epidemics
and pandemics.

Methods

A case-control study performed during the 2008/09 influenza season. Cases (n = 72)
consulted a General Practitioner with ARI, and controls with another non-respiratory
acute condition (n = 66). Data were obtained on bus or tram usage in the five days
preceding illness onset (cases) or the five days before consultation (controls) alongside
demographic details. Multiple logistic regression modelling was used to investigate
the association between bus or tram use and ARI, adjusting for potential confounders.

Results

Recent bus or tram use within five days of symptom onset was associated with an almost
six-fold increased risk of consulting for ARI (adjusted OR = 5.94 95% CI 1.33-26.5).
The risk of ARI appeared to be modified according to the degree of habitual bus and
tram use, but this was not statistically significant (1-3 times/week: adjusted OR
= 0.54 (95% CI 0.15-1.95; >3 times/week: 0.37 (95% CI 0.13-1.06).

Conclusions

We found a statistically significant association between ARI and bus or tram use in
the five days before symptom onset. The risk appeared greatest among occasional bus
or tram users, but this trend was not statistically significant. However, these data
are plausible in relation to the greater likelihood of developing protective antibodies
to common respiratory viruses if repeatedly exposed. The findings have differing implications
for the control of seasonal acute respiratory infections and for pandemic influenza.

Background

The current UK National Framework for Pandemic Influenza states that during a pandemic,
domestic travel should continue to operate normally but users should adopt good hygiene
measures, stagger journeys where possible to reduce overcrowding; and stay at home
altogether if symptomatic with pandemic influenza [1]. This advice reflects the need to maintain, as far as possible, business continuity
and near normal functioning of society, but acknowledges that some data exist about
the transmission of influenza on board public transport, notably commercial airliners
[2].

Until very recently, there were no data that directly supported or refuted an association
between the use of public ground transportation and the risk of acute respiratory
infection (ARI). The risk posed by large numbers of transient casual human contacts
has not been adequately defined. However, a recently published cohort study of hospital
healthcare workers suggested no association between serologically confirmed seasonal
influenza illness and regular public transport use; however recent use just before
the onset of respiratory illness was not evaluated [3]. A retrospective investigation following an outbreak of pandemic influenza A/H1N1
2009 amongst school children, noted no forward transmission from the index case to
contacts despite probable exposure on a school bus for up to 60 minutes [4]. The current uncertainty makes the formulation of pandemic transport policies difficult.

Methods

Study design and population

A case control methodology was employed. We recruited from patients registered at
an inner city General Practitioner (GP) surgery in Nottingham, who consulted a doctor
between December 2nd 2008 (week 49) and January 15th 2009 (week 02), a period which
coincided with known community influenza activity, and which peaked in week 51 [5]. The study involved self-completion of a questionnaire eliciting acute symptoms;
socio-demographic characteristics; health status including co-morbidities; and transport
habits generally, and specifically in relation to the period immediately preceding
the onset of illness. Patients of all ages were eligible for inclusion, provided they
were registered with the recruiting surgery, and had presented to the surgery with
an acute condition with a date of onset during the designated study period. For patients
under the age of 14, the questionnaire was completed on their behalf by a parent or
guardian. Patients presenting with chronic or recurrent conditions, visiting the doctor
for repeat prescriptions, advice, or health maintenance or monitoring (general check-ups
and screening activities) were excluded from the study. Questionnaires were either
completed by the patient at the surgery (assisted if necessary by the resident researcher,
JT), or at home, then posted back in a pre-paid envelope.

Case definition and exposure ascertainment

Cases of ARI were identified, based on clinical diagnoses made by the three participating
GPs. A case-specific questionnaire also identified any use of buses and trams in the
five-day period before symptom onset, representing a maximum putative incubation period;
and for up to five days after symptom onset, to identify instances of using public
transport whilst symptomatic, potentially exposing others. Data on demography and
habitual use of buses and trams were also collected.

Control subjects

After a patient with ARI was identified and enrolled as a case, the treating physician
was asked to identify the next presenting patient (in chronological order) with an
acute but non-respiratory condition who agreed to take part as the as a control. Controls
completed a similar questionnaire, which asked about use of buses or trams in a comparator
period, five days immediately prior to their visit to the doctor.

Potential confounders

The following risk factors were evaluated as potential confounders: age [categorised
as (0-24 yrs), (25-45 yrs), (46-65 yrs), (>65 years) to avoid creating age bands with
missing data], which potentially influences immune status; gender; number of children
in the household (all suggested to be associated with the risk of ARI); socioeconomic
status, based on the 2007 Indices of Multiple Deprivation for each individual's area
of residence (median electoral enumeration area-level IMD scores within each individual's
sub-postcode of residence) [6]; self-reported co-morbidities (diabetes, cardiovascular disease, chronic lung disease,
chronic renal disease); smoking status (current and ex-smokers for <10 years vs. stopped
smoking >10 yrs and never-smokers); and influenza vaccination status for winter 2008/09.

Power calculation

To attain statistical power of 80 percent at 5% significance, it was estimated that
184 study participants would be needed (92 cases and 92 controls) to detect an odds
ratio of 2.5, based on previous estimates of the size of association [3]. The calculations assumed that about 21 percent of Nottingham's population use public
transport (buses or trams) based on Department for Transport data [7].

Ethical approval and consent

Ethical approval for this study was obtained from Leicestershire, Northamptonshire
and Rutland Research Ethics Committee. All participants gave verbal consent before
enrolment and were provided with written information.

Statistical analysis

A univariable logistic regression analysis was carried out to investigate the association
between potential risk factors and consultation for ARI. Multivariable analysis using
a multiple logistic regression model was used to assess the strength of association
between bus or tram use in the five days prior to symptom onset (cases) or consultation
(controls) [binary categorical variable (yes/no)]. We also examined the relation between
habitual frequency of public transport use (<once/week, 1-3 times/week, and >3 times/week)
and ARI consultation. Frequency of public transport use was also modelled separately
as a continuous variable to assess trends. Results have been expressed as odds ratios
(OR) with 95% confidence intervals (CI). Age, gender and co-morbidity were included
as a priori confounders (Model 1). Other variables included in the multivariable analysis (Model
2) were those that were statistically significant (p < 0.05) risk factors for ARI
in univariable logistic regression analyses, or which modified the unadjusted OR for
the main exposure variable (recent use of public transport) by at least ± 10% in a
bivariate model (bivariate data available on request). Individuals providing incomplete
responses were excluded from the analyses. We also tested for interactions between
frequency of habitual public transport use, and recent use of public transport on
the risk of ARI using the likelihood ratio test. All analyses were carried out using
Stata® 10 (StataCorp, College Station, TX, USA).

Although we chose a period when community influenza activity had risen above baseline
[5], our case definition was clinically based and it is highly likely that our cases
of ARI included influenza and a range of other respiratory viruses. We chose a putative
incubation period of five days and accordingly recorded public transport use in the
five days before symptom onset as the likely window in which cases might have acquired
their current infection from a fellow traveller, and a matching period prior to GP
consultation in controls with non-respiratory conditions. We chose controls with other
non-respiratory acute conditions because, if most controls were consulting with chronic
conditions, this might have biased sampling towards patients less able or less willing
to use public transport.

Results and Discussion

During the study period (Dec 2nd 2008 - 15th Jan 2009) we identified and obtained information by questionnaire from 72 patients
with ARI and 66 controls with other acute non-respiratory conditions.

The median age of the sample population was 49 years (interquartile range: 24). Table
1 summarises the characteristics of cases and controls. Cases were more likely to be
older, males, living with children and to have higher co-morbidity. Cases also appeared
to be less frequent users of public transport use but this effect was not statistically
significant when frequency of habitual public transport use was modelled as a continuous
variable (p-trend = 0.845).

Table 2 presents the crude and adjusted odds ratios for the association between public transport
use and acquisition of ARI. The univariate analysis showed that cases were 10 percent
more likely to have travelled by public transport in the five days before symptom
onset than controls (unadjusted OR: 1.10, 95% CI: 0.55-2.21). This association was
not statistically significant. After adjusting for age, gender and co-morbidity (Model
1), cases were still 10 percent more likely than controls to have travelled by public
transport in the five days before symptoms, but once again, this association was not
statistically significant (adjusted OR: 1.09, 95% CI: 0.50-2.38).

Table 2. Odds ratios for the association between bus/tram use and ARI (n = 127)

Model 2 also adjusted for deprivation, child cohabitants, flu vaccination and habitual
public transport use in addition to a priori confounders; this time the strength of the association increased, with cases nearly
six times more likely to have travelled by public transport in the five days before
symptoms; this was statistically significant (adjusted OR: 5.94, 95% CI: 1.33-26.47).
After taking into account age, gender, co-morbidity, child cohabitants, flu vaccination
and deprivation, there was still no statistically significant association between
frequency of habitual public transport use and risk of consultation for ARI (p-trend
= 0.057). Nevertheless, when examining frequency of habitual public transport use
as a categorical variable, there was a trend towards a decreased risk of ARI consultation
in persons who were more frequent habitual users (1-3 uses/week: adjusted OR = 0.54
95% CI: 0.15-1.95; >3 uses/week: adjusted OR = 0.37 95% CI: 0.13-1.06). The results
of a separate logistic regression to explore the association between frequency of
habitual public transport use and recent use are presented in Additional file 1; frequent habitual users were more likely to have been recent users but inclusion
of habitual use in Model 2 nevertheless improved the overall fit compared with Model
1. We observed a significant interaction between regularity of public transport use
and recent use on the risk of ARI (p = 0.019). We were unable to perform a complete
stratified analysis by frequency of public transport use to explore this interaction
further, because of the small sample size. However we present a limited stratified
analysis in Additional file 2, which is consistent with our key finding that infrequent habitual use of public
transport poses the greatest risk of ARI.

Additional file 1.Relationship between frequency of habitual public transport use and recent use. The results of a separate logistic regression to explore the association between
frequency of habitual public transport use and recent use (n = 131).

One of the most controversial issues in pandemic preparedness is the potential benefit
conferred by public health measures, including social distancing strategies such as
the closure of mass transportation systems [8,9]. No clear consensus has yet been reached about whether mass transportation systems
should be closed during a pandemic; and the mildness of the influenza A/H1N1 pandemic
in 2009 (which did not trigger transport closures) offers little prospect of shedding
further light on this issue. When considering the possible policy impact, there is
often confusion between the potential public health effects of closing urban transportation
during a pandemic (thereby delaying population spread), versus the individual benefit
of avoiding public transport (reduction in individual risk of infection). Much will
also depend upon whether individuals will change their behaviour during a severe pandemic,
by avoiding using public transport whilst symptomatic.

In this study we set out to explore the association between recent public transport
use and the likelihood of acquiring acute respiratory infection (ARI) at an individual
level. We found a significant association between ARI consultation and recent use
of public transport; however, because of the small study size, the confidence intervals
are wide and the magnitude of risk is not clearly defined. Furthermore, we detected
a trend suggesting that the absolute risk of public transport in relation to ARI may
be modified by frequency of habitual use, the risk being decreased among the most
regular users. However the study lacked statistical power to explore this fully, using
multiplicative modelling terms.

Our findings may suggest that whilst use of public transport in the winter potentially
exposes travellers to respiratory viruses and increases the risk of ARI, the risk
is offset among regular users who either acquire immunity against a range of respiratory
viruses (or partial immunity sufficient to produce asymptomatic infections), presumably
because they are more frequently exposed; or because they develop compensatory behaviours
that reduce risk. An alternative methodological hypothesis would be that habitual
users of public transport are exposed to respiratory viruses earlier in the winter
season and so may have acquired protective immunity by the time this study began in
early December.

If true, the implication of these findings for the 'normal' winter respiratory virus
season is that occasional users of public have the greatest risk of acquiring ARI.
The implications for pandemic preparedness may be somewhat different. Given a novel
virus, against which there is lower background population immunity, the attenuating
effect of regular public transport use would be diminished and the individual risk
might be driven more by recent use of public transport and less by habitual patterns
of usage. Thus the same protective effect of regular bus and tram use may not be present.

This study has a number of strengths and limitations. We used GP consultations for
ARI as a proxy for 'all ARI' and acknowledge that because we selected only those ARIs,
which necessitated medical attention (or selecting patients more likely to consult
a GP with ARI), the findings should be interpreted carefully. Nevertheless, experienced
primary care physicians identified all cases of ARI; their symptoms were cross-checked
by the questionnaire tool and so misclassification bias seems highly unlikely. However
without virological confirmation it is not possible to describe the range of underlying
respiratory virus aetiologies in the cases in the study; thus the findings, while
generalisable, are not specific to influenza. Controls were selected as the next patient
with an acute non-respiratory condition, as determined by the chronological order
of appointments in the practice. This may have introduced some bias if persons were
seen in order of severity rather than by booking order. It is possible that if control
patients with a non-respiratory complaint (e.g. worsening cardiac failure) in fact
had underlying respiratory virus aetiology, this might have under-estimated the risk
of public transport use. This study was performed in Nottingham where in general terms
public transport use is more closely related to affluence than is the case in larger
cities (e.g. London) with more extensive urban mass transportation networks. We also
lacked data on subjects' normal working environments (e.g. lone working or in close
contact with many people). However we adjusted for deprivation score in the multivariate
analysis, which should account, to some extent, for affluence and job type. Whilst
we obtained data on frequency of habitual public transport use, we did not obtain
data on time of use (e.g. rush hour vs. off-peak) and passenger density may affect
the likelihood of exposure to an infectious traveller. The study was somewhat underpowered
due to the time and resource restrictions imposed by an undergraduate project. As
participants were not asked whether they had acquired ARI symptoms earlier in the
flu season, post-infection immunity in controls manifesting as sub-clinical ARI was
not investigated. We were unable to address asymptomatic infection in the current
study.

There are few published data available, against which this study can be meaningfully
compared. Studies of transmission on board aircraft are not comparable because of
differences in the number of 'passenger exchanges' per hour (very low compared with
buses and trams), duration of journey, and ventilation [2]. The study by Kar-Purthayaska et al. concludes that transmission of pandemic influenza
did not occur on board a school coach. However, these data are not strictly comparable
because the population was less heterogeneous than on public transport, the two school
groups may have remained separated, 'passenger exchange' was far lower and the outbreak
occurred in summer, albeit with a journey time of 60 minutes [4]. In addition pandemic influenza A/H1N1 has been associated with a very high rate
of asymptomatic infection in children [10]; so many may already have been immune or may have acquired asymptomatic infection
following exposure. The most relevant comparator study, by Williams and colleagues,
assessed the influence of regular public transport use on the risk of serologically
confirmed influenza in hospital healthcare workers, finding a risk ratio of 1.06 (95%
CI 0.69-1.63) in the 2006/07 winter season [3]. These investigators did not however report any findings about the frequency of habitual
public transport use and did not investigate the influence of public transport use
in the period immediately preceding illness onset. Our findings add new detail in
relation to the possible role of public transport in relation to the acquisition of
infection during a relevant incubation period and suggest that the frequency of habitual
public transport use ought to be explored further in future studies.

Although causality can never be firmly proven on the basis of a small observational
study, the effects we observed are biologically plausible including the diminution
of risk with increasing habitual travel frequency. Buses and trams are generally poorly
ventilated carriages of people sitting and standing in close proximity (particularly
during peak travel periods) who, if travelling whilst symptomatic and exhibiting poor
hand hygiene and cough etiquette, could spread respiratory virus infections via direct
or indirect contact. Frequent public transport users regularly exposed to respiratory
pathogens may be more likely to develop protective immunity. However, there still
seems to be a risk associated with bus or tram use related to the period immediately
preceding symptom onset. During a pandemic, when a novel respiratory virus is in circulation,
the protective effect of habitual regular bus or tram use may be much reduced. Although
small and limited in scope, this study nevertheless suggests that a larger more detailed
investigation would be appropriate.

Conclusions

The findings of this study suggest that recent use of public buses and trams is a
significant individual risk factor for the acquisition of ARI (leading to GP consultation)
in winter; this risk may be altered by frequency of habitual use but this requires
further evaluation. The findings support current public advice to exercise good respiratory
hygiene and existing pandemic guidance to refrain from making unnecessary journeys
by public transport when symptomatic. The findings do not support the effectiveness
of suspending mass urban transport systems as a pandemic countermeasure aimed at reducing
or slowing population spread because, whatever the relevance of public transport is
to individual-level risk, household exposure most likely poses a greater threat [3].

List of Abbreviations

Competing interests

JSN-V-T holds an honorary consultant contract with the Funder and is a member of the
UK Scientific Advisory Group for Emergencies (SAGE).

Authors' contributions

JSN-V-T, JEE, ACH, JG and JT conceived and designed the study. JT, JEE and AH designed
the questionnaire. JT, CJP, SK and AH executed the study. JT, JG, AH and PRM analysed
the data. JT, PRM, JEE, and JSN-V-T wrote the manuscript; all other authors contributed
to the manuscript and have read and approved the final version. JSN-V-T and PRM act
as guarantors of the data.

Authors Information

Joy Troko is an undergraduate medical student at the University of Nottingham, and
contributed to this work as part of an intercalated BMedSci degree.

Acknowledgements

We thank the staff of St Luke's Surgery, Nottingham, for kind assistance with data
collection; Sharon Figgens, for data entry and verification; Deborah Mohda, Keith
Neal, Richard Puleston, Elaine Gadd, and Martyn Regan, for helpful comments. We thank
the UK Health Protection Agency for funding this study from its Pump Priming and Small
Initiatives Fund.

References

Pandemic Flu. A national framework for responding to an influenza pandemic. London: Department of Health; 2007:79-80.